The CD4 (T4 molecule, which is a surface glycoprotein on a subset of T lymphocytes (referred to as T4 lymphocytes) is involved in Class II (Ia) MHC recognition and appears to be the physiological receptor for one or more monomorphic regions of class II MHC. Meuer, S. et al., Proceedings of the National Academy of Sciences, U.S.A., 79:4395-4399 (1982); Biddison, W. et al., J. Exp. Med., 156:1065-1076 (1982); Gay, D. et al., Nature, 328: 626-629 (1987).
Human CD4 is also the receptor for the gp120 envelope glycoprotein of the human immunodeficiency virus (HIV) and is essential for virus entry into the host cell, and for membrane fusion, which both contribute to cell-to-cell transmission of the virus and to its cytopathic effects. Klatzmann, D., et al., Science, 225: 59-63 (1984); Dalgleish, A. G., et al., Nature, 312: 763-766 (1984); Sattentau, Q., et al., Science, 234: 1120-1123 (1986); McDougal, J. S., et al., J. Immunol., 137: 2937-2944 (1986); McDougal, J. S. et al., Science, 231: 382-385 (1986); Maddon, P. J., et al., Cell, 47: 333-348 (1986); Sodroski, J., et al., Nature, 322: 470-474 (1986); Lifson, J., et al., Nature, 323: 725-728 (1986). Sequence analysis of CD4 has suggested an evolutionary origin from a structure with four immunoglobulin-related domains. Clark, S., et al. Proc. Natl. Acad. Sci., 84: 1649-1653 (1987); Littman, D. R., et al., Nature, 325: 453-455 (1987). Only the two NH.sub.2 -terminal domains are required to mediate HIV gp120 binding. Traunecker, A., et al.. Nature, 331: 84-86 (1988); Berger, E. A., et al. Proc. Natl. Acad. Sci. USA, 85: 2357-2361 (1988); Richardson, N. E., et al., Proc. Natl. Acad. Sci. USA, in press.
Considerable effort has been expended in studying the CD4-gp120 interaction and in trying to interfere with or inhibit that interaction, in an attempt to provide a means by which the life threatening effects of HIV infection can be slowed or reversed. Several groups have focused their efforts on the ability of soluble CD4 (T4) protein to interfere with infection of cells by HIV and its subsequent effects. Hussey, R. E. et al., Nature, 331:78-81 (1988); Fisher, R. A. et al., Nature, 331:76-78 (1988); Deen, K. C. et al., Nature, 331:82-84 (1988); Traunecker, A. et al., Nature, 331:84-86 (1988). A means by which to prevent HIV infection of T4 lymphocytes (i.e., helper and inducer T lymphocytes), which make up approximately 60-80% of the total circulating T lymphocyte population, would be of great value, particularly in light of the fact that HIV infection of such cells can cause total collapse of the immune system. Curran, J. et al., Science, 229:11352-1357 (1985); Weiss, R. et al., Nature, 324:572-575 (1986).